Personalized genetic testing

Abstract

The present disclosure provides methods and systems for personalized genetic testing of a subject. In some embodiments, a sequencing assay is performed on a biological sample from the subject, which then leads to genetic information related to the subject. Next, nucleic acid molecules are array-synthesized or selected based on the genetic information derived from data of the sequencing assay. At least some of the nucleic acid molecules may then be used in an assay which may provide additional information on one or more biological samples from the subject or a biological relative of the subject.

1 - 30 . (canceled) 
     
     
         31 . A method for personalized genetic testing, comprising:
 (a) sequencing nucleic acid molecules from at least one biological sample of a subject to generate sequencing data;   (b) computer processing said sequencing data to identify a plurality of nucleic acid sequences having a set of genetic variants, wherein a genetic variant of said set of genetic variants is identified based on a number of reads comprising said genetic variant which exceed a first threshold;   (c) obtaining a probe set comprising a plurality of nucleic acid probe molecules having said plurality of nucleic acid sequences or complements thereof, wherein said plurality of nucleic acid probe molecules are configured to selectively enrich or amplify sequences comprising said set of genetic variants over other sequences in said at least one biological sample;   (d) using said probe set to selectively enrich or amplify sequences comprising said set of genetic variants over other sequences in an additional biological sample from said subject, to generate a sequencing library; and   (e) subjecting said sequencing library to sequencing to identify a presence or absence of at least a subset of said set of genetic variants in said additional biological sample from said subject, wherein said genetic variant of said set of genetic variants is identified as present based on a number of reads comprising said genetic variant which exceed a second threshold, wherein said second threshold is higher than the first threshold, and wherein a sequencing depth of said sequencing of (e) is greater than a sequencing depth of said sequencing of (a).   
     
     
         32 . The method of  claim 31 , wherein said at least one biological sample or said additional sample is a tissue sample or a blood sample. 
     
     
         33 . The method of  claim 32 , wherein said blood sample is a plasma sample. 
     
     
         34 . The method of  claim 32 , wherein said tissue sample is a tumor biopsy sample. 
     
     
         35 . The method of  claim 31 , wherein said sequencing of (a) comprises (i) exome sequencing, (ii) sequencing a panel of genes, (iii) whole genome sequencing, and/or (iv) sequencing a population of complementary deoxyribonucleic acid molecules derived from ribonucleic acid molecules. 
     
     
         36 . The method of  claim 31 , wherein said nucleic acids from at least one biological sample comprise DNA or RNA. 
     
     
         37 . The method of  claim 36 , wherein said DNA is cell-free DNA. 
     
     
         38 . The method of  claim 36 , wherein said RNA is cell-free RNA. 
     
     
         39 . The method of  claim 31 , wherein said at least one biological sample is obtained at a first time point and the additional sample is obtained at a same time point. 
     
     
         40 . The method of  claim 31 , wherein said at least one biological sample is obtained at a first time point and the additional sample is obtained at a second time point subsequent to said first time point. 
     
     
         41 . The method of claim  13 , wherein said at least one biological sample and said additional sample include the same biological sample. 
     
     
         42 . The method of  claim 31 , wherein said plurality of nucleic acid sequences having said set of genetic variants comprises one or more members selected from the group consisting of: (i) single nucleotide polymorphisms, (ii) insertions or deletions, (iii) copy number variations, and (iv) structural variations. 
     
     
         43 . The method of  claim 31 , further comprising outputting a report that identifies said presence or absence of said at least said subset of said genetic variants in said subject. 
     
     
         44 . The method of  claim 31 , wherein further comprising outputting a report that identifies a health condition based on said presence or absence of said at least said subset of said genetic variants in said subject. 
     
     
         45 . The method of  claim 31 , wherein said probe set comprises primers for amplifying the nucleic acid sequences. 
     
     
         46 . The method of  claim 31 , wherein said probe set comprises hybrid capture probes. 
     
     
         47 . The method of  claim 31 , wherein said set of genetic variants identified in sequence data are determined with respect to a reference. 
     
     
         48 . The method of  claim 31 , wherein said subject has or is suspected of having cancer. 
     
     
         49 . The method of  claim 31 , wherein said subject suffers from cancer and is being treated for cancer. 
     
     
         50 . The method of  claim 31 , further comprising repeating (d) and (e) on a second additional sample. 
     
     
         51 . The method of  claim 50 , wherein said second additional sample and said additional sample are obtained at different time points. 
     
     
         52 . The method of  claim 31 , wherein said probe set comprises nucleic acid molecules having oligonucleotide-directed genomic content comprising: (i) at least one variable portion from a result of said sequence data of (a) and (ii) at least one fixed portion independent of said result of said sequence data of (a). 
     
     
         53 . The method of  claim 52 , wherein said at least one fixed portion is selected from a group consisting of one or more of: (i) cancer driver genes, (ii) genes involved in the pharmacogenomics of cancer drugs, (iii) genes involved in Mendelian immunological diseases, (iv) genes related to inherited forms of cancer, (v) genes associated with tumor escape from a targeted or immune cancer therapy, (vi) HLA typing, (vii) variants common in the population and used by B-allele methods to detect structural variation, and any combination thereof.